The gut microbiome of healthy co-twins from inflammatory bowel disease (IBD)-discordant twin pairs has been found to display IBD-like signatures, researchers reported in Gastroenterology.

The investigators included participants from 2 cohorts in the cross-sectional study: IBD twins and healthy co-twins (aged ≥16 years) from the Twin Cohort for the Study of (Pre)clinical IBD in the Netherlands (TWIN) study, and healthy control participants and unrelated patients with IBD (aged 8-84 years) from the Dutch Microbiome Project. The healthy control participants from the Dutch Microbiome Project had comparable age, sex, and body mass index (BMI) but smoked less frequently compared with all twins, and the unrelated patients with IBD were older and had a higher BMI compared with the TWIN cohort.

The study authors obtained fecal samples from 99 twins from 51 twin pairs; 495 healthy age-, sex-, and BMI-matched control participants; and 99 unrelated patients with IBD. They performed their analysis in 2 steps: first, they compared the healthy co-twins with their IBD twins (within twin pairs comparison), and then they compared the gut microbiome of healthy co-twins, IBD twins, and unrelated patients with IBD with that of the healthy control participants.


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The researchers observed no significant differences in the relative abundance of species and pathways among healthy co-twins and their IBD twins (false discovery rate [FDR] <0.1). A total of 13, 19, and 18 species and 78, 105, and 153 pathways were differentially abundant in healthy co-twins, IBD twins, and unrelated patients with IBD, respectively, compared with healthy control participants (FDR <0.1). Of these, 8/19 (42.1%) and 1/18 (5.6%) species and 37/105 (35.2%) and 30/153 (19.6%) pathways overlapped among healthy co-twins and IBD-twins, and healthy co-twins and unrelated patients with IBD, respectively.

“Taken all together, an increase in potentially pathogenic species and pro-inflammatory pathways was noted in the gut microbiome of healthy cotwins of IBD-discordant twin pairs compared to healthy controls,” stated the study authors. “A substantial proportion of these differences are shared with IBD twins and unrelated IBD patients.”

The researchers noted that a larger sample size could have increased the power to detect more subtle differences in microbiome composition and that multicollinearity prevented them from correcting for the use of IBD medication and stool consistency.

“We found that the gut microbiome of healthy cotwins from IBD-discordant twin pairs displays IBD-like signatures, both at a taxonomic and functional level,” the investigators commented. “The gut microbiome of these individuals at increased risk of developing IBD displays similarities to the gut microbiome of their IBD-affected twins and unrelated IBD patients, and is different from healthy controls. These IBD-like microbiome signatures could be a reflection of a shared genetic background and environment and might precede IBD development. However, longitudinal studies are needed to infer a causal relationship.”

Disclosures: Some of the authors reported affiliations with pharmaceutical and biotechnology companies. Please see the original reference for a full list of disclosures.

Reference

Brand EC, Klaassen MAY, Gacesa R, et al. Healthy cotwins share gut microbiome signatures with their inflammatory bowel disease twins and unrelated patients. Gastroenterology. Published online January 19, 2021. doi:10.1053/j.gastro.2021.01.030